| Coronavirus 3′ stem-loop II-like motif (s2m) | |
|---|---|
 Predictedsecondary structure andsequence conservation of s2m | |
| Identifiers | |
| Symbol | s2m |
| Rfam | RF00164 |
| Other data | |
| RNA type | Cis-reg |
| Domain(s) | Eukaryota;Viruses |
| SO | SO:0000233 |
| PDB structures | PDBe |
TheCoronavirus 3′ stem-loop II-like motif (also known as s2m) is asecondary structure motif identified in the3′ untranslated region (3′UTR) ofastrovirus,coronavirus and equinerhinovirusgenomes.[1][2] Its function is unknown, but various viral 3′ UTR regions have been found to play roles inviral replication and packaging.
This motif appears to be conserved in bothnucleotide sequence andsecondary structure folding indicating a strong evolutionary selection for itsconservation. The presence of this conserved motif in different viral families is suggested to be the result of at least two separaterecombination events.[2] To date s2m has been described in four families of positive sense single-stranded RNA viruses;Astroviridae,Caliciviridae,Picornaviridae andCoronaviridae. The viruses that contain s2m can infect a wide range of higher vertebrates, including birds, bats, horses, dogs and humans, and display different tissue tropisms.[3][4] There seems to be a xenologue of s2m in a number of only distantly related insect species.[5]
Other RNA families identified in the coronavirus include thecoronavirus frameshifting stimulation element, thecoronavirus packaging signal and thecoronavirus 3′ UTR pseudoknot.
Functionally during host invasion by viral RNA, it appears that s2m first binds one or more proteins as a mechanism for the viral RNA to substitute host protein synthesis. This has also been seen in s2m RNA macromolecular substitution of ribosomal RNA folds. The s2m RNA element are also effective targets for the design of anti-viral drugs and antisense oligonucleotides.[6][2]
Potential interacting human microRNA targets of SARS-CoV-2 that share similarity with those of influenza A virus H1N1 was identified as therapeutic targets.[7]
The overall X-ray (2.7-Å) crystal structure of the s2m SARS-CoV-1 RNA and[2] is different from theSARS-CoV-2 s2m secondary structure determined by NMR.[8] Long-distance interactions between the 5′ UTR and s2m in SARS-CoV-2 genomic RNA have been suggested.[9]
During COVID-19 pandemic in 2020, many genomic sequences of Australian SARS‐CoV‐2 isolates have deletions or mutations (29742G>A or 29742G>U; "G19A" or "G19U") in the s2m, suggesting that RNA recombination may have occurred in this RNA element. 29742G("G19"), 29744G("G21"), and 29751G("G28") were predicted as recombination hotspots.[10] 29742G>U mutation was also linked to travellers returning from Iran to Australia and New Zealand.[11] In three patients inDiamond Princess cruise, two mutations, 29736G > T and 29751G > T ("G13" and "G28") were found in s2m of SARS-CoV-2, as "G28" was predicted as recombination hotspots in Australian SARS-CoV-2 mutants. This result suggests that s2m of SARS-CoV-2 isRNA recombination/mutation hotspot rather than a conserved RNA motif found in other coronaviruses.[12]
Molecular dynamics simulations shows that both S2M variants, 29734G>C (G11C) and 29742G>U (G19U), of SARS-CoV-2 change RNA structure stability, raising questions as to the functional relevance of s2m in SARS-CoV-2 replication.[13]
